Phosphatemic effect of cinacalcet in kidney transplant recipients with persistent hyperparathyroidism.
BACKGROUND
In kidney transplant recipients, persistent hyperparathyroidism leads to hypercalcemia and increased urinary phosphorus excretion. The calcimimetic drug cinacalcet effectively decreases parathyroid hormone (PTH) levels and corrects hypercalcemia in these patients. The purpose of the present study is to examine the effect of cinacalcet treatment on determinants of renal phosphorus reabsorption under steady-state conditions.


METHODS
Open-label prospective uncontrolled trial.


METHODS
10 stable kidney transplant recipients with persistent hyperparathyroidism.


METHODS
Cinacalcet, 30 and 60 mg/d, for 2 weeks.


METHODS
Changes in urinary phosphorus excretion in timed urine samples, intact and carboxy-terminal (C-term) fibroblast growth factor 23 (FGF-23), intact PTH, venous pH, and bicarbonate values at defined intervals over 24 hours.


RESULTS
Cinacalcet decreased renal phosphorus excretion in the first 8 hours by 30% to 40%, but not from 8 to 24 hours after drug administration. Serum phosphorus levels normalized in all patients. Cinacalcet markedly decreased plasma intact PTH levels (60%; P < 0.001). Cinacalcet also decreased mean intact FGF-23 levels from 67 +/- 8 (SE) to 51 +/- 5 and to 54 +/- 6 pg/mL (P < 0.001) and mean C-term FGF-23 levels from 108 +/- 15 to 87 +/- 9 and to 101 +/- 9 RU/mL (P < 0.01), respectively. There was high correlation between intact FGF-23 and C-term FGF-23 levels (r = 0.598; P < 0.001). Acid-base status was unchanged.


CONCLUSIONS
This is a small study and does not examine the long-term effect of cinacalcet treatment.


CONCLUSIONS
Cinacalcet effectively corrected urinary phosphate wasting in kidney transplant recipients, resulting in normalization of serum phosphorus levels. The phosphatemic effects of cinacalcet correlated with a marked decrease in the phosphaturic hormone PTH, rather than with a change in FGF-23 levels or acid-base status, highlighting the importance of PTH in posttransplantation hypophosphatemia.
Serra
Andreas L
AL
Clinic for Nephrology, University Hospital, Zürich, Switzerland. andreas.serra@usz.ch
Wuhrmann
Claudia
C
Wüthrich
Rudolf P
RP
D000069449:Cinacalcet; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D006801:Humans; D006961:Hyperparathyroidism / Q000097:blood / Q000188:drug therapy* / Q000652:urine*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood / Q000652:urine*; D011446:Prospective Studies
C000717427:FGF23 protein, human; D009281:Naphthalenes; D010281:Parathyroid Hormone; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000069449:Cinacalcet